DCC is specifically required for the survival of retinal ganglion and displaced amacrine cells in the developing mouse retina

Genetically modified mice lacking the β2 laminin chain (β2null), the γ3 laminin chain (γ3 null), or both β2/γ3 chains (compound null) were produced. The development of tyrosine hydroxylase (TH) immunoreactive neurons in these mouse lines was studied between birth and postnatal day (P) 20. Compared to wild type mice, no alterations were seen in γ3 null mice. In β2 null mice, however, the large, type I TH neurons appeared later in development, were at a lower density and had reduced TH immunoreactivity, although TH process number and size were not altered. In the compound null mouse, the same changes were observed together with reduced TH process outgrowth. Surprisingly, in the smaller, type II TH neurons, TH immunoreactivity was increased in laminin-deficient compared to wild type mice. Other retinal defects we observed were a patchy disruption of the inner limiting retinal basement membrane and a disoriented growth of Müller glial cells. Starburst and AII type amacrine cells were not apparently altered in laminin-deficient relative to wild type mice. We postulate that laminin-dependent developmental signals are conveyed to TH amacrine neurons through intermediate cell types, perhaps the Müller glial cell and/or the retinal ganglion cell.

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A quantitative analysis of the effects of excitatory neurotoxins on retinal ganglion cells in the chick

Visual Neuroscience ◽

10.1017/s0952523800003369 ◽

1990 ◽

Vol 4 (3) ◽

pp. 217-223 ◽

Cited By ~ 23

Author(s):

Ngoh Ngoh Tung ◽

Ian G. Morgan ◽

David Ehrlich

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Amacrine Cells ◽

Small Cells ◽

Retinal Ganglion ◽

Chick Retina ◽

Area 5 ◽

Different Types ◽

Displaced Amacrine Cells ◽

Series Of Experiments

AbstractThe present study examines the differential effects of three excitotoxins, kainic acid (KA), N-methyl-D-aspartate (NMDA), and α-amino-2,3-amino-2,3-dihydro-5- methyl-3-oxo-4- isoxazolepropanoic acid (AMPA) on neurons within the genglion cell layer (GCL) of the chick retina. Two-day-old chicks were given a single, 5 μl, intravitreal injection of KA, NMDA, or AMPA at a range of doses. Following treatment with 40 nmol KA, there was a 21% loss of neurons in the GCL. At 200 nmol KA, the loss increased to 46%. Exposure to KA eliminated mainly small neurons of soma area 5–15μm2, and medium-sized ganglion cells of soma area 15–25μm2. Large ganglion cells (>25μ,2) remained unaffected. The vast majority of small cells were probably displaced amarcrine cells. At a does of 3000 nmol NMDA, no further loss of cells was evident. Exposure to 200 nmol AMPA resulted in a 30% loss of large and some medium-sized ganglion cells. In a further series of experiments, exposure to excitotoxin was followed by a retinal scratch, which eliminated retinal ganglion cells within the axotomized region. The results indicate that only a small proportion of displaced amacrine cells are destroyed by NMDA and AMPA, whereas virtually all displaced amarine cells are sensitive to KA. The findings of this study indicate the existence of subclasses of ganglion cells with specificity towards different types of excitatory amino acids (EAA).

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Glycinergic input of widefield, displaced amacrine cells of the mouse retina

The Journal of Physiology ◽

10.1113/jphysiol.2009.171207 ◽

2009 ◽

Vol 587 (15) ◽

pp. 3831-3849 ◽

Cited By ~ 18

Author(s):

Sriparna Majumdar ◽

Jan Weiss ◽

Heinz Wässle

Keyword(s):

Amacrine Cells ◽

Mouse Retina ◽

Displaced Amacrine Cells

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PTEN Expression Regulates Gap Junction Connectivity in the Retina

Frontiers in Neuroanatomy ◽

10.3389/fnana.2021.629244 ◽

2021 ◽

Vol 15 ◽

Author(s):

Ashley M. Chen ◽

Shaghauyegh S. Azar ◽

Alexander Harris ◽

Nicholas C. Brecha ◽

Luis Pérez de Sevilla Müller

Keyword(s):

Gap Junction ◽

Retinal Ganglion Cells ◽

Vision Loss ◽

Ganglion Cells ◽

Dendritic Structure ◽

Amacrine Cells ◽

Mouse Retina ◽

Retinal Ganglion ◽

Cell Coupling ◽

Cell Degeneration

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten+/– retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson’s, and Alzheimer’s diseases.

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Evidence for novel transient clusters of cholinergic ganglion cells in the neonatal mouse retina

10.1101/2019.12.27.888792 ◽

2019 ◽

Author(s):

Jean de Montigny ◽

Vidhyasankar Krishnamoorthy ◽

Fernando Rozenblit ◽

Tim Gollisch ◽

Evelyne Sernagor

Keyword(s):

Ganglion Cells ◽

Amacrine Cells ◽

Bipolar Cells ◽

Neonatal Mouse ◽

Mouse Retina ◽

Retinal Ganglion ◽

Electrical Imaging ◽

Subplate Neurons ◽

Starburst Amacrine Cells ◽

Cholinergic Cell

AbstractWaves of spontaneous activity sweep across the neonatal mouse retinal ganglion cell (RGC) layer, driven by directly interconnected cholinergic starburst amacrine cells (the only known retinal cholinergic cells) from postnatal day (P) 0-10, followed by waves driven by glutamatergic bipolar cells. We found transient clusters of cholinergic RGC-like cells around the optic disc during the period of cholinergic waves. They migrate towards the periphery between P2-9 and then they disappear. Pan-retinal multielectrode array recordings reveal that cholinergic wave origins follow a similar developmental center-to-periphery pattern. Electrical imaging unmasks hotspots of dipole electrical activity occurring in the vicinity of wave origins. We propose that these activity hotspots are sites for wave initiation and are related to the cholinergic cell clusters, reminiscent of activity in transient subplate neurons in the developing cortex, suggesting a universal hyper-excitability mechanism in developing CNS networks during the critical period for brain wiring.

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Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina

Cells ◽

10.3390/cells9030530 ◽

2020 ◽

Vol 9 (3) ◽

pp. 530 ◽

Cited By ~ 3

Author(s):

Seema Banerjee ◽

Qin Wang ◽

Chung Him So ◽

Feng Pan

Keyword(s):

Edge Detection ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Public Health Problem ◽

Amacrine Cells ◽

The United States ◽

Mouse Retina ◽

Major Public Health Problem ◽

Retinal Ganglion ◽

Firing Patterns

Myopia is a major public health problem, affecting one third of the population over 12 years old in the United States and more than 80% of people in Hong Kong. Myopia is attributable to elongation of the eyeball in response to defocused images that alter eye growth and refraction. It is known that the retina can sense the focus of an image, but the effects of defocused images on signaling of population of retinal ganglion cells (RGCs) that account either for emmetropization or refractive errors has still to be elucidated. Thorough knowledge of the underlying mechanisms could provide insight to understanding myopia. In this study, we found that focused and defocused images can change both excitatory and inhibitory conductance of ON alpha, OFF alpha and ON–OFF retinal ganglion cells in the mouse retina. The firing patterns of population of RGCs vary under the different powers of defocused images and can be affected by dopamine receptor agonists/antagonists’ application. OFF-delayed RGCs or displaced amacrine cells (dACs) with time latency of more than 0.3 s had synchrony firing with other RGCs and/or dACs. These spatial synchrony firing patterns between OFF-delayed cell and other RGCs/dACs were significantly changed by defocused image, which may relate to edge detection. The results suggested that defocused images induced changes in the multineuronal firing patterns and whole cell conductance in the mouse retina. The multineuronal firing patterns can be affected by dopamine receptors’ agonists and antagonists. Synchronous firing of OFF-delayed cells is possibly related to edge detection, and understanding of this process may reveal a potential therapeutic target for myopia patients.

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Antibodies against neurofilament subunits label retinal ganglion cells but not displaced amacrine cells of hamsters

Life Sciences ◽

10.1016/s0024-3205(99)00115-0 ◽

1999 ◽

Vol 64 (19) ◽

pp. 1773-1778 ◽

Cited By ~ 13

Author(s):

W.C. Kong ◽

E.Y.P. Cho

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Amacrine Cells ◽

Retinal Ganglion ◽

Displaced Amacrine Cells

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Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina

The Journal of Comparative Neurology ◽

10.1002/cne.22490 ◽

2010 ◽

Vol 518 (23) ◽

pp. 4813-4824 ◽

Cited By ~ 48

Author(s):

Luis Pérez de Sevilla Müller ◽

Michael Tri H. Do ◽

King-Wai Yau ◽

Shigang He ◽

William H. Baldridge

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Amacrine Cells ◽

Mouse Retina ◽

Retinal Ganglion

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POU6F2 Positive Retinal Ganglion Cells a Novel Group of ON-OFF Directionally Selective Subtypes in the Mouse Retina

10.1101/2020.02.28.968503 ◽

2020 ◽

Author(s):

Ying Li ◽

Jiaxing Wang ◽

Rebecca King ◽

Eldon E. Geisert

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Yellow Fluorescent Protein ◽

Corneal Thickness ◽

Amacrine Cells ◽

Molecular Signature ◽

Retinal Cell ◽

Mouse Retina ◽

Inner Plexiform Layer ◽

Retinal Ganglion

AbstractPurposePreviously we identified POU6F2 as a genetic link between central corneal thickness (CCT) and risk of open-angle glaucoma. The present study is designed to characterize the POU6F2-positive retinal ganglion cells (RGCs).MethodsThe Thy1-YFP-H mouse was used to identify the structure of POU6F2-positive RGCs in the retina. In the retina of the Thy1-YFP-H mouse approximately 3% of the RGCs were labeled with yellow fluorescent protein. These retinas were stained for POU6F2 to identify the morphology of the POU6F2 subtypes in 3D reconstructions of the labeled RGCs. Multiple retinal cell markers were also co-stained with POU6F2 to characterize the molecular signature of the POU6F2-positive RGCs. DBA/2J glaucoma models were used to test the role of POU6F2 in injury.ResultsIn the retina POU6F2 labels 32.9% of the RGCs in the DBA/2J retina (16.1% heavily and 16.8% lightly labeled). In 3D constructions of Thy1-YFP-H positive RGCs, the heavily labeled POU6F2-positive cells had dendrites in the inner plexiform layer that were bistratified and appeared to be ON-OFF directionally selective cells. The lightly labeled POU6F2 RGCs displayed 3 different dendritic distributions, with dendrites in the ON sublaminae only, OFF sublaminae only, or bistratified. The POU6F2-positive cells partially co-stained with Cdh6. The POU6F2-positive cells do not co-stain with CART and SATB2 (markers for ON-OFF directionally selective RGC), SMI32 (a marker for alpha RGCs), or ChAT and GAD67(markers for amacrine cells). The POU6F2-positive cells were sensitive to injury. In DBA/2J glaucoma model, at 8 months of age there was a 22% loss of RGCs (labeled with RBPMS) while there was 73% loss of the heavily labeled POU6F2 RGCs.ConclusionsPOU6F2 is a marker for a novel group of RGC subtypes that are ON-OFF directionally selective RGCs that are sensitive to glaucomatous injury.

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Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells

10.1101/2020.10.29.361147 ◽

2020 ◽

Author(s):

Michael D. Flood ◽

Erika D. Eggers

Keyword(s):

Light Adaptation ◽

Dynamic Range ◽

Ganglion Cells ◽

Amacrine Cells ◽

Mouse Retina ◽

Retinal Ganglion ◽

Cell Responses ◽

Light Levels ◽

Excitatory Activity ◽

Effect Of Light

AbstractAdaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses only covers ~1000 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 family – D1Rs that are expressed on horizontal cells and some bipolar and ganglion cells- and the D2 family – D2Rs that are expressed on dopaminergic amacrine cells and D4Rs that are primarily expressed on photoreceptors. However, how these receptors change the synaptic properties of the inputs to ganglion cells is not yet clear. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating D1Rs and D4Rs changed the light-evoked and spontaneous excitatory inputs to ON-sustained (ON-s) ganglion cells. We found that both D1R and D4R activation decrease the light-evoked excitatory inputs to ON-s ganglion cells, but that only the sum of activating the two receptors was similar to the effect of light adaptation to a rod-saturating background. The largest effects on spontaneous excitatory activity of both D1R and D4R agonists was on the frequency of events, suggesting that D1Rs and D4Rs are acting upstream of the ganglion cells.

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